Case scenario L1&2: Gastroesophageal Reflux Disease & Peptic Ulcer objectives ● Describe the definition, pathogenesis, clinical features, pathology (gross and microscopic features) and complications of reflux esophagitis. ● Describe the definition, main cause, pathology (gross and microscopic features) and complications (dysplasia and adenocarcinoma) of Barrett esophagus. ● Define ulcer and erosion. ● Describe the pathogenesis, pathology and clinical features of acute gastric ulcers. ● Describe the pathogenesis (H pylori, NSAID, Z-E syndrome), clinical features, pathology (gross and microscopic features) and complications (bleeding, perforation, obstruction) of chronic peptic ulcers. Black: original content Orange: Doctor notes Red: Important Grey: Extra/Robbins Green: only found in males slides Purple: Only found in females slides Editing File Lecture Content Physiological GERD reflux Esophagitis (pathological) Severe stress Acute gastritis Hyperacidity response Acute Ulcers Chronic Gastric Duodenal NSAIDs Bile Reflux H. pylori Infection Hyperacidity Esophagitis Reflux esophagitis ● Symptoms or mucosal damage produced by the abnormal reflux of gastric content into the esophagus, often chronic and relapsing. ● Esophagitis is rarely caused by anything other than reflux. ● May see complications of GERD in patients who lack typical symptoms. ● Some other causes include: ○ Infective ■ Fungal infection (common): candida albicans. ■ Viral infection: Herpes simplex and cytomegalovirus in AIDS patients. ■ Bacterial infection is very rare. ○ Physical Agent ■ Irradiation ■ Ingestion of caustic agent Gastroesophageal reflux disease Gastroesophageal reflux (GERD) A normal physiological phenomena The amount of gastric juice that experienced intermittently by most refluxes into the the esophagus people: exceeds the normal limit, causing: ● After a meal (postprandial) ● Symptoms ● Short lived ● with or without esophageal ● Asymptomatic mucosal injury ● No nocturnal symptoms ● Nocturnal symptoms Epidemiology of GERD ● 44% of americans have heartburns at least once a month (physiological type). ● 14% have weekly symptoms (GERD). ● 7% have daily symptoms (GERD). ● 80% of pregnant women have GERD. ● Hiatal hernia is present in 70% of people with GERD. Symptoms ● Typical: ○ Heartburning; retrosternal burning. ○ Regurgitation; (feeling of acidity in throat) effortless return of gastric content into the pharynx, without nausea, retching, or abdominal contractions. ● Atypical (usually in older age group): ○ Coughing: At night or during sleep ○ Chest pain: similar to Angina ○ Wheezing: Fluid return to pharynx → larynx → irritation → bronchospasm GERD Pathophysiology Abnormal Lower esophageal Increased abdominal pressure sphincter (LES) The LES prevents the gastric juice Increased pressure in the stomach from reaching the esophagus, which is compared to that of the esophagus sensitive to its acidity. allows for gastric content to reflux 1. Functional; frequent transient LES into the esophagus. relaxation 1. Obesity 2. Mechanical; hypotensive LES 2. Pregnancy 3. Food; coffee, alcohol, smoking 3. Increased gastric volume after 4. Medication; calcium channel heavy meal. blocker, CNS depressants. 5. Location: hiatal hernia (X-ray show gas behind heart) Risk Factors ● Smoking, Alcohol. ● Caffeine, fatty foods, chocolate. ● Pregnancy, obesity. ● Hiatal hernia: Herniation of a portion of the stomach into the lower thorax. Types of hiatal hernia: Sliding (more common in GERD) and rolling. Diagnosis ● If typical symptoms are present, without atypical symptoms, diagnosis is made clinically without further evaluation. ● Endoscopy (with biopsy if needed) is done rarely: ○ Patients with alarm symptoms; dysphagia, which indicated there is complications. ○ Patients who fail medication trial. ○ Those who require long-term treatment. ● 24-hour pH monitoring: ○ For establishing and excluding GERD, for patients who do not have mucosal change. GERD Complications 1- Hematemesis: the vomiting of blood. 2- Melena: black tarry stools. 3- Erosive esophagitis ● Responsible for 40-60% of GERD symptoms. ● Severity of symptoms might not match severity of esophagitis. ● Morphology: ○ Basal zone hyperplasia. ○ Elongation of lamina propria. ○ Eosinophils and neutrophils. ○ Red mucosa with erosions and ulceration. 4- Esophageal stricture ● Narrowing of esophagus, due to healing erosive esophagitis. ● May need dilation. 5- Barrett’s esophagus ● Intestinal metaplasia of the esophagus. The stratified squamous epithelium of the esophagus becomes columnar with goblet cells, in the lower esophagus. ● Patients may be asymptomatic. ● The incidence of Barrett esophagus is rising. ● Occur in 10% of individuals with symptomatic GERD. ● Most common in white males and typically presents between 40 and 60 years. ● Can only be identified through endoscopy and biopsy, due to GERD symptoms. ● Pathophysiology: Reflux acid damages the Healing in a metaplastic Could progress to lining of the esophagus process results in dysplasia and causing chronic columnar cells replacing adenocarcinoma esophagitis squamous cells Normal 5 Short segments Endoscopic image of barrett’s Long segments, Irregular Mass → adenocarcinoma esophagus: an area of red mucosa and rough processes Long segments, tongue like processes + dysplasia GERD ● Complications of Barrett’s esophagus: Dysplasia ○ Dysplasia ■ The presence of dysplasia, a preinvasive change, is associated with prolonged symptoms, longer segment length, increased patient age, and Caucasian race. ■ Low-grade dysplasia: Cytological changes e.g. nuclear Adenocarcinoma stratification, hyperchromasia and increased nuclear to Adenocarcinoma cytoplasmic ratio. ■ High-grade dysplasia: Architectural irregularities, including gland within gland, or cribriform pattern in addition to cytological changes. ○ Adenocarcinoma ■ Risk factors other than Barrett’s esophagus: tobacco and radiation. ■ The risk is reduced by diets rich in fresh fruits and vegetables. ■ Occurs in the distal third of the esophagus and may invade the adjacent gastric cardia. ■ Well to poorly differentiated adenocarcinoma. ■ Present with pain or difficulty in swallowing, progressive weight loss, hematemesis, chest pain, or vomiting. ■ Prognosis depends on the stage. 6- Squamous carcinoma ● Most common in middle and lower esophagus. ● Common in men who are heavy smokers or alcohol drinkers. ● Maybe preceded by epithelial dysplasia. ● The most common malignant tumors of the esophagus are squamous carcinoma and adenocarcinoma. Both have poor prognosis. ● Not related to GERD Treatment ● H2 receptor blockers ● Proton pump inhibitor ● May require antireflux surgery 6 Ulcers ● Erosion: is a breach in the epithelium of the mucosa only. ● Ulcer: is a breach in the mucosa of the alimentary tract extending through muscularis mucosa into submucosa or deeper. ○ Types: i. Peptic ulcer: chronic. ii. Stress ulcers: acute gastric (peptic) ulcers. ○ Pathophysiology: imbalance between aggressive factors & defensive factors: Aggressive Factors Defensive Factors H. pylori Mucus Drugs (NSAIDs) bicarbonate Acid Blood flow & Cell renewal pepsin Prostaglandins Bile salts Phospholipid Acute peptic ulcers (stress ulcers) ● Pathophysiology: ○ Part of an acute gastritis: ■ Acute response to an irritant 'chemical' injury by drugs: ● NSAIDs ● Alcohol ○ Complication of a severe stress response: ■ Severe burns (Curling's ulcer) ■ Major trauma (Cushing ulcer) ■ Cerebrovascular accidents (Cushing ulcer) ○ A result of extreme hyperacidity: ■ Zollinger-Ellison syndrome1 Location Morphology Prognosis Clinical findings: Anywhere in They range in depth from very The gastric mucosa can a. Hematemesis the stomach superficial lesions (erosion) to recover completely if the b. Melena deeper lesions that involve the person does not die from c. Iron deficiency due entire mucosal thickness (true the primary disease to chronic bleeding. ulceration) 1. A condition in which a gastrin-secreting tumour or hyperplasia of the islet cells in the pancreas causes overproduction of gastric acid, resulting in recurrent peptic ulcers. 7 Ulcers Peptic Ulcer Disease (Chronic peptic ulcer) ● Peptic ulcers are chronic, recurring lesions that occur most often in middle-aged to older adults without obvious precipitating conditions, other than chronic gastritis. ● Locations ○ May occur anywhere, often solitary in GI tract exposed to acidic gastric juices. ○ 98% located in first portion of duodenum or stomach (Ratio =4:1) ■ Gastric peptic ulcers are predominantly located near the interface of the body and antrum at lesser curvature. ■ Duodenal ulcers usually occur within a few centimeters of the pyloric valve at the anterior duodenal wall. ○ Esophagus, as a result of GERD or acid secretion by ectopic gastric mucosa. ○ Gastric mucosa within a Meckel diverticulum can result in peptic ulceration of adjacent mucosa. ■ Most common congenital abnormality of the small intestine caused by an incomplete obliteration of the vitelline duct, Simply it’s normal tissue at abnormal location, so if Gastric tissue is in the small intestine it will cause peptic ulceration of of adjacent mucosa. (More info) ○ In Zollinger-Ellison syndrome: multiple peptic ulcerations in the stomach, duodenum, and even the jejunum. ● Mucosal defences against acid attack consist of: 1) Mucus-bicarbonate barrier 2) Surface epithelium NSAIDs Disrupted by Duodeno-gastric reflux (blocking the synthesis of the prostaglandins) ( bile ) H. pylori infection1 (cytotoxins and ammonia) ● Note: 1. Helicobacter Pylori does not colonise normal